CA3198957A1 - Treatment of enpp1 deficiency and abcc6 deficiency - Google Patents

Info

Publication number

CA3198957A1

CA3198957A1 CA3198957A CA3198957A CA3198957A1 CA 3198957 A1 CA3198957 A1 CA 3198957A1 CA 3198957 A CA3198957 A CA 3198957A CA 3198957 A CA3198957 A CA 3198957A CA 3198957 A1 CA3198957 A1 CA 3198957A1

Authority

CA

Canada

Prior art keywords

subject

enpp1

per kilogram

agent

calcification

Prior art date

2020-11-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 230000007812 deficiency Effects 0.000 title claims abstract description 152
• 238000011282 treatment Methods 0.000 title abstract description 84
• 101000812677 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 claims abstract description 455
• 102100039306 Nucleotide pyrophosphatase Human genes 0.000 claims abstract description 449
• 208000004434 Calcinosis Diseases 0.000 claims abstract description 150
• 102100028187 ATP-binding cassette sub-family C member 6 Human genes 0.000 claims abstract description 149
• 230000002308 calcification Effects 0.000 claims abstract description 142
• 101000986621 Homo sapiens ATP-binding cassette sub-family C member 6 Proteins 0.000 claims abstract description 103
• 230000001575 pathological effect Effects 0.000 claims abstract description 61
• 208000004900 arterial calcification of infancy Diseases 0.000 claims abstract description 60
• 208000033173 Generalized arterial calcification of infancy Diseases 0.000 claims abstract description 59
• 201000003672 autosomal recessive hypophosphatemic rickets Diseases 0.000 claims abstract description 11
• 238000000034 method Methods 0.000 claims description 277
• 239000003795 chemical substances by application Substances 0.000 claims description 180
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 141
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 133
• 229920001184 polypeptide Polymers 0.000 claims description 132
• 208000024891 symptom Diseases 0.000 claims description 68
• 241000282414 Homo sapiens Species 0.000 claims description 52
• 208000005475 Vascular calcification Diseases 0.000 claims description 50
• 210000001519 tissue Anatomy 0.000 claims description 49
• 201000004613 Pseudoxanthoma elasticum Diseases 0.000 claims description 48
• 208000023558 pseudoxanthoma elasticum (inherited or acquired) Diseases 0.000 claims description 48
• 208000020832 chronic kidney disease Diseases 0.000 claims description 46
• 230000000694 effects Effects 0.000 claims description 40
• 235000011180 diphosphates Nutrition 0.000 claims description 31
• 108060003951 Immunoglobulin Proteins 0.000 claims description 29
• 102000018358 immunoglobulin Human genes 0.000 claims description 29
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 28
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 26
• 230000003442 weekly effect Effects 0.000 claims description 23
• 230000001965 increasing effect Effects 0.000 claims description 22
• 208000007442 rickets Diseases 0.000 claims description 22
• 210000001367 artery Anatomy 0.000 claims description 20
• 239000011575 calcium Substances 0.000 claims description 19
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 17
• 229910052791 calcium Inorganic materials 0.000 claims description 17
• 201000011510 cancer Diseases 0.000 claims description 16
• 230000033558 biomineral tissue development Effects 0.000 claims description 15
• 201000000523 end stage renal failure Diseases 0.000 claims description 15
• 108010009413 Pyrophosphatases Proteins 0.000 claims description 14
• 102000009609 Pyrophosphatases Human genes 0.000 claims description 14
• 208000011111 hypophosphatemic rickets Diseases 0.000 claims description 14
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 14
• 239000011707 mineral Substances 0.000 claims description 14
• 230000011164 ossification Effects 0.000 claims description 14
• 210000004204 blood vessel Anatomy 0.000 claims description 13
• 230000002950 deficient Effects 0.000 claims description 13
• 230000036210 malignancy Effects 0.000 claims description 12
• 208000034970 Heterotopic Ossification Diseases 0.000 claims description 11
• 230000005856 abnormality Effects 0.000 claims description 11
• 210000002808 connective tissue Anatomy 0.000 claims description 11
• 230000002159 abnormal effect Effects 0.000 claims description 10
• 125000000539 amino acid group Chemical group 0.000 claims description 10
• 210000001508 eye Anatomy 0.000 claims description 10
• 206010051714 Calciphylaxis Diseases 0.000 claims description 9
• 238000009825 accumulation Methods 0.000 claims description 9
• 210000004177 elastic tissue Anatomy 0.000 claims description 9
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 8
• 230000003197 catalytic effect Effects 0.000 claims description 8
• 230000001684 chronic effect Effects 0.000 claims description 8
• 210000003734 kidney Anatomy 0.000 claims description 8
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 7
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 7
• 239000003112 inhibitor Substances 0.000 claims description 7
• 210000004446 longitudinal ligament Anatomy 0.000 claims description 7
• 210000003141 lower extremity Anatomy 0.000 claims description 7
• 102000009027 Albumins Human genes 0.000 claims description 6
• 108010088751 Albumins Proteins 0.000 claims description 6
• 101710163270 Nuclease Proteins 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 238000012423 maintenance Methods 0.000 claims description 6
• 210000001525 retina Anatomy 0.000 claims description 6
• 201000004569 Blindness Diseases 0.000 claims description 5
• 230000004393 visual impairment Effects 0.000 claims description 5
• 208000005598 Angioid Streaks Diseases 0.000 claims description 4
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
• 208000033825 Chorioretinal atrophy Diseases 0.000 claims description 4
• 201000011180 Dental Pulp Calcification Diseases 0.000 claims description 4
• 208000012528 Juvenile dermatomyositis Diseases 0.000 claims description 4
• 208000000913 Kidney Calculi Diseases 0.000 claims description 4
• 208000013836 Malacoplakia Diseases 0.000 claims description 4
• 206010029148 Nephrolithiasis Diseases 0.000 claims description 4
• 229940127355 PCSK9 Inhibitors Drugs 0.000 claims description 4
• 208000008117 Salivary Gland Calculi Diseases 0.000 claims description 4
• 206010039710 Scleroderma Diseases 0.000 claims description 4
• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 4
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 4
• 208000006568 Urinary Bladder Calculi Diseases 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 201000006800 aortic valve disease 1 Diseases 0.000 claims description 4
• 210000000748 cardiovascular system Anatomy 0.000 claims description 4
• 201000010415 childhood type dermatomyositis Diseases 0.000 claims description 4
• 201000001883 cholelithiasis Diseases 0.000 claims description 4
• 201000001981 dermatomyositis Diseases 0.000 claims description 4
• 201000010934 exostosis Diseases 0.000 claims description 4
• 208000001130 gallstones Diseases 0.000 claims description 4
• 238000001631 haemodialysis Methods 0.000 claims description 4
• 230000000322 hemodialysis Effects 0.000 claims description 4
• 201000010930 hyperostosis Diseases 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 201000007094 prostatitis Diseases 0.000 claims description 4
• 201000008261 skin carcinoma Diseases 0.000 claims description 4
• 201000004595 synovitis Diseases 0.000 claims description 4
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
• 230000002381 testicular Effects 0.000 claims description 4
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
• 206010022562 Intermittent claudication Diseases 0.000 claims description 3
• 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims description 3
• 101710180553 Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims description 3
• 206010047571 Visual impairment Diseases 0.000 claims description 3
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
• 208000024980 claudication Diseases 0.000 claims description 3
• 230000002037 soft tissue calcification Effects 0.000 claims description 3
• 208000029257 vision disease Diseases 0.000 claims description 3
• 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 2
• 206010060823 Choroidal neovascularisation Diseases 0.000 claims description 2
• 239000012528 membrane Substances 0.000 claims description 2
• 208000002111 Eye Abnormalities Diseases 0.000 claims 1
• 101100238304 Mus musculus Morc1 gene Proteins 0.000 claims 1
• 208000012641 Pigmentation disease Diseases 0.000 claims 1
• 238000011065 in-situ storage Methods 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 110
• 201000010099 disease Diseases 0.000 abstract description 65
• 208000035475 disorder Diseases 0.000 abstract description 45
• 210000004872 soft tissue Anatomy 0.000 abstract description 8
• 238000001727 in vivo Methods 0.000 abstract 1
• 210000002381 plasma Anatomy 0.000 description 69
• 108090000623 proteins and genes Proteins 0.000 description 64
• 235000018102 proteins Nutrition 0.000 description 53
• 102000004169 proteins and genes Human genes 0.000 description 53
• 210000000988 bone and bone Anatomy 0.000 description 39
• 230000035772 mutation Effects 0.000 description 37
• 210000004027 cell Anatomy 0.000 description 31
• 108010076504 Protein Sorting Signals Proteins 0.000 description 30
• 102000004042 Fibroblast Growth Factor-23 Human genes 0.000 description 28
• 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 description 28
• 229910019142 PO4 Inorganic materials 0.000 description 27
• 235000021317 phosphate Nutrition 0.000 description 27
• 102000004190 Enzymes Human genes 0.000 description 26
• 108090000790 Enzymes Proteins 0.000 description 26
• 235000001014 amino acid Nutrition 0.000 description 26
• 239000003814 drug Substances 0.000 description 26
• 229940088598 enzyme Drugs 0.000 description 26
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 26
• 210000002966 serum Anatomy 0.000 description 26
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 25
• 229940125994 INZ-701 Drugs 0.000 description 25
• 239000010452 phosphate Substances 0.000 description 25
• 229940024606 amino acid Drugs 0.000 description 23
• 210000004369 blood Anatomy 0.000 description 23
• 239000008280 blood Substances 0.000 description 23
• 229940079593 drug Drugs 0.000 description 23
• 108020001507 fusion proteins Proteins 0.000 description 23
• 102000037865 fusion proteins Human genes 0.000 description 23
• 230000014509 gene expression Effects 0.000 description 23
• 108020004414 DNA Proteins 0.000 description 21
• 150000001413 amino acids Chemical class 0.000 description 21
• 208000005050 Familial Hypophosphatemic Rickets Diseases 0.000 description 19
• 239000002773 nucleotide Substances 0.000 description 19
• 210000003491 skin Anatomy 0.000 description 19
• 238000012360 testing method Methods 0.000 description 19
• 239000000047 product Substances 0.000 description 18
• 230000009467 reduction Effects 0.000 description 18
• 241001465754 Metazoa Species 0.000 description 17
• 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 17
• 230000004927 fusion Effects 0.000 description 17
• -1 nucleotide triphosphates Chemical class 0.000 description 17
• 229960005069 calcium Drugs 0.000 description 16
• 230000002255 enzymatic effect Effects 0.000 description 16
• 239000000203 mixture Substances 0.000 description 16
• 101150095012 ABCC6 gene Proteins 0.000 description 15
• UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 15
• 230000036541 health Effects 0.000 description 15
• 208000005368 osteomalacia Diseases 0.000 description 15
• 208000002193 Pain Diseases 0.000 description 14
• 238000004458 analytical method Methods 0.000 description 13
• 239000002243 precursor Substances 0.000 description 13
• 208000031878 X-linked hypophosphatemia Diseases 0.000 description 12
• 201000003674 autosomal dominant hypophosphatemic rickets Diseases 0.000 description 12
• 230000006870 function Effects 0.000 description 12
• 241000124008 Mammalia Species 0.000 description 11
• 101150011046 NPP1 gene Proteins 0.000 description 11
• 230000027455 binding Effects 0.000 description 11
• 230000008859 change Effects 0.000 description 11
• 150000001875 compounds Chemical class 0.000 description 11
• 238000005259 measurement Methods 0.000 description 11
• 230000004044 response Effects 0.000 description 11
• 238000012216 screening Methods 0.000 description 11
• 125000006850 spacer group Chemical group 0.000 description 11
• 239000000758 substrate Substances 0.000 description 11
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 10
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 10
• 101100080092 Phytophthora capsici NLP1 gene Proteins 0.000 description 10
• 238000001514 detection method Methods 0.000 description 10
• 239000012634 fragment Substances 0.000 description 10
• 210000002216 heart Anatomy 0.000 description 10
• 206010006002 Bone pain Diseases 0.000 description 9
• 102000003982 Parathyroid hormone Human genes 0.000 description 9
• 108090000445 Parathyroid hormone Proteins 0.000 description 9
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
• 230000004071 biological effect Effects 0.000 description 9
• 238000011156 evaluation Methods 0.000 description 9
• 230000033001 locomotion Effects 0.000 description 9
• 150000007523 nucleic acids Chemical class 0.000 description 9
• 238000006467 substitution reaction Methods 0.000 description 9
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 8
• 230000003247 decreasing effect Effects 0.000 description 8
• 108010067341 ectonucleotide pyrophosphatase phosphodiesterase 1 Proteins 0.000 description 8
• 238000002347 injection Methods 0.000 description 8
• 239000007924 injection Substances 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 125000003729 nucleotide group Chemical group 0.000 description 8
• 239000000199 parathyroid hormone Substances 0.000 description 8
• 229960001319 parathyroid hormone Drugs 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 210000001364 upper extremity Anatomy 0.000 description 8
• 210000002700 urine Anatomy 0.000 description 8
• 101150017770 ENPP1 gene Proteins 0.000 description 7
• 206010020772 Hypertension Diseases 0.000 description 7
• 230000002411 adverse Effects 0.000 description 7
• 239000000427 antigen Substances 0.000 description 7
• 108091007433 antigens Proteins 0.000 description 7
• 102000036639 antigens Human genes 0.000 description 7
• 239000000090 biomarker Substances 0.000 description 7
• 238000003745 diagnosis Methods 0.000 description 7
• 102000039446 nucleic acids Human genes 0.000 description 7
• 108020004707 nucleic acids Proteins 0.000 description 7
• 210000000056 organ Anatomy 0.000 description 7
• 239000001226 triphosphate Substances 0.000 description 7
• 235000011178 triphosphate Nutrition 0.000 description 7
• 208000029663 Hypophosphatemia Diseases 0.000 description 6
• 241000699666 Mus <mouse, genus> Species 0.000 description 6
• 239000004365 Protease Substances 0.000 description 6
• 206010040026 Sensory disturbance Diseases 0.000 description 6
• 238000012076 audiometry Methods 0.000 description 6
• 230000008468 bone growth Effects 0.000 description 6
• 230000007547 defect Effects 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 230000018109 developmental process Effects 0.000 description 6
• 230000002526 effect on cardiovascular system Effects 0.000 description 6
• 208000028208 end stage renal disease Diseases 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 230000005847 immunogenicity Effects 0.000 description 6
• 210000003739 neck Anatomy 0.000 description 6
• RWOAVOYBVRQNIZ-BFHYXJOUSA-N p-nitrophenyl thymidine 5'-monophosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OC=2C=CC(=CC=2)[N+]([O-])=O)[C@@H](O)C1 RWOAVOYBVRQNIZ-BFHYXJOUSA-N 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 230000002792 vascular Effects 0.000 description 6
• 208000006820 Arthralgia Diseases 0.000 description 5
• 229940122361 Bisphosphonate Drugs 0.000 description 5
• 241000283690 Bos taurus Species 0.000 description 5
• 206010013975 Dyspnoeas Diseases 0.000 description 5
• 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 5
• 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• 208000029725 Metabolic bone disease Diseases 0.000 description 5
• 206010028570 Myelopathy Diseases 0.000 description 5
• 206010049088 Osteopenia Diseases 0.000 description 5
• 206010033733 Papule Diseases 0.000 description 5
• 108091005804 Peptidases Proteins 0.000 description 5
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 5
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 5
• 206010037779 Radiculopathy Diseases 0.000 description 5
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 150000004663 bisphosphonates Chemical class 0.000 description 5
• 230000017531 blood circulation Effects 0.000 description 5
• 238000004422 calculation algorithm Methods 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 238000002591 computed tomography Methods 0.000 description 5
• 230000008021 deposition Effects 0.000 description 5
• 230000002068 genetic effect Effects 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 208000035824 paresthesia Diseases 0.000 description 5
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 5
• 230000003285 pharmacodynamic effect Effects 0.000 description 5
• 230000036470 plasma concentration Effects 0.000 description 5
• 239000013612 plasmid Substances 0.000 description 5
• 230000002028 premature Effects 0.000 description 5
• 108091008146 restriction endonucleases Proteins 0.000 description 5
• 238000012552 review Methods 0.000 description 5
• 210000000278 spinal cord Anatomy 0.000 description 5
• 238000007920 subcutaneous administration Methods 0.000 description 5
• 230000009885 systemic effect Effects 0.000 description 5
• 239000013598 vector Substances 0.000 description 5
• 208000010392 Bone Fractures Diseases 0.000 description 4
• 206010070918 Bone deformity Diseases 0.000 description 4
• 208000006029 Cardiomegaly Diseases 0.000 description 4
• 206010050217 Cervical radiculopathy Diseases 0.000 description 4
• 208000016216 Choristoma Diseases 0.000 description 4
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
• 206010011878 Deafness Diseases 0.000 description 4
• 108700024394 Exon Proteins 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• 208000026350 Inborn Genetic disease Diseases 0.000 description 4
• 102000007330 LDL Lipoproteins Human genes 0.000 description 4
• 108010007622 LDL Lipoproteins Proteins 0.000 description 4
• 208000020221 Short stature Diseases 0.000 description 4
• 208000032023 Signs and Symptoms Diseases 0.000 description 4
• HSCJRCZFDFQWRP-RDKQLNKOSA-N UDP-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-RDKQLNKOSA-N 0.000 description 4
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
• 229930003316 Vitamin D Natural products 0.000 description 4
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
• 229940069428 antacid Drugs 0.000 description 4
• 239000003159 antacid agent Substances 0.000 description 4
• 230000001174 ascending effect Effects 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 238000007470 bone biopsy Methods 0.000 description 4
• 230000002092 calcimimetic effect Effects 0.000 description 4
• 229960005084 calcitriol Drugs 0.000 description 4
• GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 4
• 239000001506 calcium phosphate Substances 0.000 description 4
• 229960001714 calcium phosphate Drugs 0.000 description 4
• 229910000389 calcium phosphate Inorganic materials 0.000 description 4
• 235000011010 calcium phosphates Nutrition 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 230000000295 complement effect Effects 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 239000003246 corticosteroid Substances 0.000 description 4
• 229940109239 creatinine Drugs 0.000 description 4
• 230000004064 dysfunction Effects 0.000 description 4
• 230000007717 exclusion Effects 0.000 description 4
• 210000003414 extremity Anatomy 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 210000004247 hand Anatomy 0.000 description 4
• 230000010370 hearing loss Effects 0.000 description 4
• 231100000888 hearing loss Toxicity 0.000 description 4
• 208000016354 hearing loss disease Diseases 0.000 description 4
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 4
• 230000001771 impaired effect Effects 0.000 description 4
• 210000002414 leg Anatomy 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 238000002483 medication Methods 0.000 description 4
• 230000037230 mobility Effects 0.000 description 4
• 238000010172 mouse model Methods 0.000 description 4
• 210000003205 muscle Anatomy 0.000 description 4
• 230000002093 peripheral effect Effects 0.000 description 4
• 230000000306 recurrent effect Effects 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 230000008719 thickening Effects 0.000 description 4
• 230000014616 translation Effects 0.000 description 4
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
• 235000019166 vitamin D Nutrition 0.000 description 4
• 239000011710 vitamin D Substances 0.000 description 4
• 150000003710 vitamin D derivatives Chemical class 0.000 description 4
• 229940046008 vitamin d Drugs 0.000 description 4
• JARGNLJYKBUKSJ-KGZKBUQUSA-N (2r)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydrobromide Chemical compound Br.OC(=O)[C@H](N)CCC(=O)N[C@H](CO)C(=O)NCC(O)=O JARGNLJYKBUKSJ-KGZKBUQUSA-N 0.000 description 3
• LVXLCZPTUBQNHH-UHFFFAOYSA-N 2-amino-5-[[1-(carboxymethylamino)-3-(2-chloro-1,1,2-trifluoroethyl)sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound OC(=O)C(N)CCC(=O)NC(CSC(F)(F)C(F)Cl)C(=O)NCC(O)=O LVXLCZPTUBQNHH-UHFFFAOYSA-N 0.000 description 3
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
• 206010069632 Bladder dysfunction Diseases 0.000 description 3
• 208000020084 Bone disease Diseases 0.000 description 3
• 241000282472 Canis lupus familiaris Species 0.000 description 3
• 108091026890 Coding region Proteins 0.000 description 3
• 108020004705 Codon Proteins 0.000 description 3
• 208000032170 Congenital Abnormalities Diseases 0.000 description 3
• 208000009283 Craniosynostoses Diseases 0.000 description 3
• 206010049889 Craniosynostosis Diseases 0.000 description 3
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
• 108010036949 Cyclosporine Proteins 0.000 description 3
• 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 3
• 102100036093 Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Human genes 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• 208000000381 Familial Hypophosphatemia Diseases 0.000 description 3
• 241000282326 Felis catus Species 0.000 description 3
• 206010017076 Fracture Diseases 0.000 description 3
• 108010070675 Glutathione transferase Proteins 0.000 description 3
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 3
• 101000897035 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 3
• 101000876377 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Proteins 0.000 description 3
• 102000008100 Human Serum Albumin Human genes 0.000 description 3
• 108091006905 Human Serum Albumin Proteins 0.000 description 3
• 208000037147 Hypercalcaemia Diseases 0.000 description 3
• 206010051232 Hyperphosphaturia Diseases 0.000 description 3
• 102000000853 LDL receptors Human genes 0.000 description 3
• 108010001831 LDL receptors Proteins 0.000 description 3
• 208000007101 Muscle Cramp Diseases 0.000 description 3
• 208000008238 Muscle Spasticity Diseases 0.000 description 3
• 208000010428 Muscle Weakness Diseases 0.000 description 3
• 206010028372 Muscular weakness Diseases 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 206010030113 Oedema Diseases 0.000 description 3
• 101150004854 PHEX gene Proteins 0.000 description 3
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
• 108700008242 S-(2-chloro-1,1,2-trifluoroethyl)glutathione Proteins 0.000 description 3
• 101000995829 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Nucleotide pyrophosphatase Proteins 0.000 description 3
• 230000037182 bone density Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 210000004899 c-terminal region Anatomy 0.000 description 3
• 159000000007 calcium salts Chemical class 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 230000029087 digestion Effects 0.000 description 3
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
• 229940000406 drug candidate Drugs 0.000 description 3
• 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 3
• 238000001976 enzyme digestion Methods 0.000 description 3
• 238000002641 enzyme replacement therapy Methods 0.000 description 3
• 230000029142 excretion Effects 0.000 description 3
• 208000030533 eye disease Diseases 0.000 description 3
• 206010016256 fatigue Diseases 0.000 description 3
• 108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 description 3
• 208000016361 genetic disease Diseases 0.000 description 3
• 208000014092 hereditary hypophosphatemic rickets Diseases 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 230000000148 hypercalcaemia Effects 0.000 description 3
• 208000030915 hypercalcemia disease Diseases 0.000 description 3
• 230000028993 immune response Effects 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 210000003127 knee Anatomy 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 210000003041 ligament Anatomy 0.000 description 3
• 150000002632 lipids Chemical class 0.000 description 3
• 230000004777 loss-of-function mutation Effects 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 230000007659 motor function Effects 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 238000012014 optical coherence tomography Methods 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 230000006503 pathological mineralization Effects 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 239000011574 phosphorus Substances 0.000 description 3
• 229910052698 phosphorus Inorganic materials 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 235000019419 proteases Nutrition 0.000 description 3
• 230000017854 proteolysis Effects 0.000 description 3
• 210000003625 skull Anatomy 0.000 description 3
• 208000018198 spasticity Diseases 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 208000011580 syndromic disease Diseases 0.000 description 3
• 238000002604 ultrasonography Methods 0.000 description 3
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
• GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 2
• KUBWJGWIWGGEPZ-UHFFFAOYSA-N 1-[amino(ethoxy)phosphoryl]oxy-4-nitrobenzene Chemical compound CCOP(N)(=O)OC1=CC=C([N+]([O-])=O)C=C1 KUBWJGWIWGGEPZ-UHFFFAOYSA-N 0.000 description 2
• XRILCFTWUCUKJR-INFSMZHSSA-N 2'-3'-cGAMP Chemical compound C([C@H]([C@H]1O)O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=NC=NC(N)=C5N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H]2N1C=NC2=C1NC(N)=NC2=O XRILCFTWUCUKJR-INFSMZHSSA-N 0.000 description 2
• 102100022464 5'-nucleotidase Human genes 0.000 description 2
• 102100025683 Alkaline phosphatase, tissue-nonspecific isozyme Human genes 0.000 description 2
• 101100225890 Aplysia californica ENPP gene Proteins 0.000 description 2
• 101000823233 Arabidopsis thaliana ABC transporter B family member 6 Proteins 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
• BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
• 208000011491 Bowing of the legs Diseases 0.000 description 2
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
• 208000025721 COVID-19 Diseases 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 206010061809 Cervix carcinoma stage 0 Diseases 0.000 description 2
• 206010009696 Clumsiness Diseases 0.000 description 2
• 108700010070 Codon Usage Proteins 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 102000012422 Collagen Type I Human genes 0.000 description 2
• 108010022452 Collagen Type I Proteins 0.000 description 2
• 206010011703 Cyanosis Diseases 0.000 description 2
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
• 238000007399 DNA isolation Methods 0.000 description 2
• 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 2
• 206010013886 Dysaesthesia Diseases 0.000 description 2
• 241000283073 Equus caballus Species 0.000 description 2
• 241000701533 Escherichia virus T4 Species 0.000 description 2
• 206010064571 Gene mutation Diseases 0.000 description 2
• 208000010300 Genu Varum Diseases 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• 201000003676 Hereditary hypophosphatemic rickets with hypercalciuria Diseases 0.000 description 2
• 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 2
• 101000574445 Homo sapiens Alkaline phosphatase, tissue-nonspecific isozyme Proteins 0.000 description 2
• 108090000144 Human Proteins Proteins 0.000 description 2
• 102000003839 Human Proteins Human genes 0.000 description 2
• 206010020590 Hypercalciuria Diseases 0.000 description 2
• 201000002980 Hyperparathyroidism Diseases 0.000 description 2
• 206010061216 Infarction Diseases 0.000 description 2
• 206010062061 Knee deformity Diseases 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 208000032912 Local swelling Diseases 0.000 description 2
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
• 208000034819 Mobility Limitation Diseases 0.000 description 2
• 102400000743 NPP Human genes 0.000 description 2
• 101800002690 NPP Proteins 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 208000009469 Ossification of Posterior Longitudinal Ligament Diseases 0.000 description 2
• 229940122392 PCSK9 inhibitor Drugs 0.000 description 2
• 241001504519 Papio ursinus Species 0.000 description 2
• 208000031481 Pathologic Constriction Diseases 0.000 description 2
• 208000037273 Pathologic Processes Diseases 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108010050808 Procollagen Proteins 0.000 description 2
• 208000003251 Pruritus Diseases 0.000 description 2
• 208000035977 Rare disease Diseases 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 102000007562 Serum Albumin Human genes 0.000 description 2
• 108010071390 Serum Albumin Proteins 0.000 description 2
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
• 206010058660 Spinal ligament ossification Diseases 0.000 description 2
• 208000002847 Surgical Wound Diseases 0.000 description 2
• 108010006785 Taq Polymerase Proteins 0.000 description 2
• 206010044016 Tooth abscess Diseases 0.000 description 2
• 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 229960005305 adenosine Drugs 0.000 description 2
• 238000001042 affinity chromatography Methods 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 210000003423 ankle Anatomy 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000001458 anti-acid effect Effects 0.000 description 2
• 210000000709 aorta Anatomy 0.000 description 2
• 230000036528 appetite Effects 0.000 description 2
• 235000019789 appetite Nutrition 0.000 description 2
• 229960001230 asparagine Drugs 0.000 description 2
• 235000009582 asparagine Nutrition 0.000 description 2
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
• 239000012620 biological material Substances 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 230000036765 blood level Effects 0.000 description 2
• 230000037180 bone health Effects 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 210000001775 bruch membrane Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 235000020964 calcitriol Nutrition 0.000 description 2
• 239000011612 calcitriol Substances 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 210000000845 cartilage Anatomy 0.000 description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 230000001149 cognitive effect Effects 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 238000012790 confirmation Methods 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 229960001334 corticosteroids Drugs 0.000 description 2
• 229960004397 cyclophosphamide Drugs 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 238000000502 dialysis Methods 0.000 description 2
• 238000006471 dimerization reaction Methods 0.000 description 2
• 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 206010014910 enthesopathy Diseases 0.000 description 2
• 238000007824 enzymatic assay Methods 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 230000024924 glomerular filtration Effects 0.000 description 2
• 230000013632 homeostatic process Effects 0.000 description 2
• 229920001519 homopolymer Polymers 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 230000003301 hydrolyzing effect Effects 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000000415 inactivating effect Effects 0.000 description 2
• 230000007574 infarction Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 206010022437 insomnia Diseases 0.000 description 2
• 230000008069 intimal proliferation Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000001155 isoelectric focusing Methods 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 230000007803 itching Effects 0.000 description 2
• 208000017169 kidney disease Diseases 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 2
• 229960003136 leucine Drugs 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 230000000116 mitigating effect Effects 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 230000003387 muscular Effects 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 231100000062 no-observed-adverse-effect level Toxicity 0.000 description 2
• 238000005457 optimization Methods 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 208000001040 ossification of the posterior longitudinal ligament of the spine Diseases 0.000 description 2
• 238000002578 otoscopy Methods 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 230000009054 pathological process Effects 0.000 description 2
• 230000007310 pathophysiology Effects 0.000 description 2
• 239000000816 peptidomimetic Substances 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• 230000001323 posttranslational effect Effects 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-M 0.000 description 2
• 238000002203 pretreatment Methods 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 210000000512 proximal kidney tubule Anatomy 0.000 description 2
• 235000021251 pulses Nutrition 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 101150027996 smb1 gene Proteins 0.000 description 2
• 108091006284 sodium-phosphate co-transporters Proteins 0.000 description 2
• 208000002320 spinal muscular atrophy Diseases 0.000 description 2
• 230000036262 stenosis Effects 0.000 description 2
• 208000037804 stenosis Diseases 0.000 description 2
• 238000010254 subcutaneous injection Methods 0.000 description 2
• 239000007929 subcutaneous injection Substances 0.000 description 2
• 230000009469 supplementation Effects 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 238000002626 targeted therapy Methods 0.000 description 2
• 210000002435 tendon Anatomy 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 210000000115 thoracic cavity Anatomy 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• 108091007466 transmembrane glycoproteins Proteins 0.000 description 2
• 102000035160 transmembrane proteins Human genes 0.000 description 2
• 108091005703 transmembrane proteins Proteins 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 230000003313 weakening effect Effects 0.000 description 2
• JWUBBDSIWDLEOM-XHQRYOPUSA-N (3e)-3-[(2e)-2-[1-(6-hydroxy-6-methylheptan-2-yl)-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol Chemical compound C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2\C1=C\C=C1/CC(O)CCC1=C JWUBBDSIWDLEOM-XHQRYOPUSA-N 0.000 description 1
• VVJYUAYZJAKGRQ-UHFFFAOYSA-N 1-[4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C(O)C1 VVJYUAYZJAKGRQ-UHFFFAOYSA-N 0.000 description 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
• 208000035657 Abasia Diseases 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
• 108010082126 Alanine transaminase Proteins 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 101100133992 Amycolatopsis sp Aaar gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010060965 Arterial stenosis Diseases 0.000 description 1
• 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
• 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
• 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
• 241000228212 Aspergillus Species 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 101710154607 Azurocidin Proteins 0.000 description 1
• 244000063299 Bacillus subtilis Species 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• 229940022962 COVID-19 vaccine Drugs 0.000 description 1
• 241001678559 COVID-19 virus Species 0.000 description 1
• 101100180402 Caenorhabditis elegans jun-1 gene Proteins 0.000 description 1
• 235000021318 Calcifediol Nutrition 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 108090000317 Chymotrypsin Proteins 0.000 description 1
• UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
• 208000034656 Contusions Diseases 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 102000012410 DNA Ligases Human genes 0.000 description 1
• 108010061982 DNA Ligases Proteins 0.000 description 1
• 108010017826 DNA Polymerase I Proteins 0.000 description 1
• 102000004594 DNA Polymerase I Human genes 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
• 102100022375 Dentin matrix acidic phosphoprotein 1 Human genes 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010052273 Dystrophic calcification Diseases 0.000 description 1
• 102100021962 Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Human genes 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 108010042407 Endonucleases Proteins 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010074860 Factor Xa Proteins 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 102000016359 Fibronectins Human genes 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 241001123946 Gaga Species 0.000 description 1
• 206010017577 Gait disturbance Diseases 0.000 description 1
• 241000272496 Galliformes Species 0.000 description 1
• 206010018341 Gliosis Diseases 0.000 description 1
• KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
• 108010037370 Glu-Glu-Glu-Glu-Glu-Glu-Glu-Pro-Arg-Gly-Asp-Thr Proteins 0.000 description 1
• 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
• 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
• 102100034471 H(+)/Cl(-) exchange transporter 5 Human genes 0.000 description 1
• 101150105462 HIS6 gene Proteins 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 241000711549 Hepacivirus C Species 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 208000028782 Hereditary disease Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000804518 Homo sapiens Cyclin-D-binding Myb-like transcription factor 1 Proteins 0.000 description 1
• 101000901629 Homo sapiens Dentin matrix acidic phosphoprotein 1 Proteins 0.000 description 1
• 101000897063 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Proteins 0.000 description 1
• 101000710225 Homo sapiens H(+)/Cl(-) exchange transporter 5 Proteins 0.000 description 1
• 101000941866 Homo sapiens Leucine-rich repeat neuronal protein 2 Proteins 0.000 description 1
• 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
• 101001055531 Homo sapiens Matrix extracellular phosphoglycoprotein Proteins 0.000 description 1
• 101001128634 Homo sapiens NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Proteins 0.000 description 1
• 101000671649 Homo sapiens Upstream stimulatory factor 2 Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 208000004044 Hypesthesia Diseases 0.000 description 1
• 208000013038 Hypocalcemia Diseases 0.000 description 1
• VWFWJPJMAFRNET-MQWMPURMSA-N IACI Chemical compound C1=CC=C2C([C@@H](O)[C@@H]3CC4CCN3C[C@@H]4CC)=CC=NC2=C1NC(=O)C1=CC([125I])=C(N=[N+]=[N-])C=C1O VWFWJPJMAFRNET-MQWMPURMSA-N 0.000 description 1
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 206010062018 Inborn error of metabolism Diseases 0.000 description 1
• 208000012659 Joint disease Diseases 0.000 description 1
• 101710172072 Kexin Proteins 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 102100032653 Leucine-rich repeat neuronal protein 2 Human genes 0.000 description 1
• 208000009829 Lewy Body Disease Diseases 0.000 description 1
• 201000002832 Lewy body dementia Diseases 0.000 description 1
• 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 1
• 102100026142 Matrix extracellular phosphoglycoprotein Human genes 0.000 description 1
• 208000024556 Mendelian disease Diseases 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000029578 Muscle disease Diseases 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 102100032194 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Human genes 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 208000008457 Neurologic Manifestations Diseases 0.000 description 1
• 101100395023 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-7 gene Proteins 0.000 description 1
• 108020004485 Nonsense Codon Proteins 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
• 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
• 241000282579 Pan Species 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 241000235648 Pichia Species 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 229920000388 Polyphosphate Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 101710160093 Progressive ankylosis protein Proteins 0.000 description 1
• 108010044159 Proprotein Convertases Proteins 0.000 description 1
• 102000006437 Proprotein Convertases Human genes 0.000 description 1
• 108091008109 Pseudogenes Proteins 0.000 description 1
• 102000057361 Pseudogenes Human genes 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 108091006575 SLC34A3 Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 102000000890 Somatomedin B domains Human genes 0.000 description 1
• 108050007913 Somatomedin B domains Proteins 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 108090000787 Subtilisin Proteins 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• 108090001109 Thermolysin Proteins 0.000 description 1
• 102100036407 Thioredoxin Human genes 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 208000024799 Thyroid disease Diseases 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
• 108030003004 Triphosphatases Proteins 0.000 description 1
• 206010044688 Trisomy 21 Diseases 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• CTCBPRXHVPZNHB-VQFZJOCSSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate;(2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O CTCBPRXHVPZNHB-VQFZJOCSSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 210000000577 adipose tissue Anatomy 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 229960004539 alirocumab Drugs 0.000 description 1
• KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229940027030 altoprev Drugs 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 229940059756 arava Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
• 208000037691 autosomal recessive 1 hypophosphatemic rickets Diseases 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 210000002469 basement membrane Anatomy 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 230000018678 bone mineralization Effects 0.000 description 1
• 230000008416 bone turnover Effects 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 210000001217 buttock Anatomy 0.000 description 1
• QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical class [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 1
• 238000005251 capillar electrophoresis Methods 0.000 description 1
• 150000001720 carbohydrates Chemical group 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 230000007211 cardiovascular event Effects 0.000 description 1
• 210000001715 carotid artery Anatomy 0.000 description 1
• 238000005277 cation exchange chromatography Methods 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 201000007455 central nervous system cancer Diseases 0.000 description 1
• 210000002230 centromere Anatomy 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 239000003593 chromogenic compound Substances 0.000 description 1
• 229960002376 chymotrypsin Drugs 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 238000003759 clinical diagnosis Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000010941 cobalt Substances 0.000 description 1
• 229910017052 cobalt Inorganic materials 0.000 description 1
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 102000006834 complement receptors Human genes 0.000 description 1
• 108010047295 complement receptors Proteins 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 229940066901 crestor Drugs 0.000 description 1
• GOHCTCOGYKAJLZ-UHFFFAOYSA-N ctep Chemical compound CC=1N(C=2C=CC(OC(F)(F)F)=CC=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 GOHCTCOGYKAJLZ-UHFFFAOYSA-N 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 230000001351 cycling effect Effects 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• 210000003298 dental enamel Anatomy 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 238000002224 dissection Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 238000002592 echocardiography Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000035194 endochondral ossification Effects 0.000 description 1
• 230000007368 endocrine function Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 229960002027 evolocumab Drugs 0.000 description 1
• 230000003090 exacerbative effect Effects 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000003811 finger Anatomy 0.000 description 1
• 102000034287 fluorescent proteins Human genes 0.000 description 1
• 108091006047 fluorescent proteins Proteins 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 230000037433 frameshift Effects 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• 230000005021 gait Effects 0.000 description 1
• YTVGSCZIHGRVAV-UHFFFAOYSA-N ganoderic acid c1 Chemical compound CC12CCC(=O)C(C)(C)C1CC(O)C1=C2C(=O)CC2(C)C(C(CC(=O)CC(C)C(O)=O)C)CC(=O)C21C YTVGSCZIHGRVAV-UHFFFAOYSA-N 0.000 description 1
• 210000001156 gastric mucosa Anatomy 0.000 description 1
• 229940062737 gengraf Drugs 0.000 description 1
• 230000007387 gliosis Effects 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 201000004502 glycogen storage disease II Diseases 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 238000012074 hearing test Methods 0.000 description 1
• 230000004217 heart function Effects 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 230000000004 hemodynamic effect Effects 0.000 description 1
• 208000012285 hip pain Diseases 0.000 description 1
• 230000002962 histologic effect Effects 0.000 description 1
• 230000003284 homeostatic effect Effects 0.000 description 1
• 239000000710 homodimer Substances 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 102000043635 human AZU1 Human genes 0.000 description 1
• 102000057100 human USF2 Human genes 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 201000005991 hyperphosphatemia Diseases 0.000 description 1
• 230000000705 hypocalcaemia Effects 0.000 description 1
• 208000034783 hypoesthesia Diseases 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 230000008629 immune suppression Effects 0.000 description 1
• 230000006058 immune tolerance Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 230000001861 immunosuppressant effect Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229940073062 imuran Drugs 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 208000016245 inborn errors of metabolism Diseases 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000036545 infantile onset glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 230000032631 intramembranous ossification Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 208000024765 knee pain Diseases 0.000 description 1
• 238000009533 lab test Methods 0.000 description 1
• 239000006101 laboratory sample Substances 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 229940063725 leukeran Drugs 0.000 description 1
• 230000029226 lipidation Effects 0.000 description 1
• 229940002661 lipitor Drugs 0.000 description 1
• 229940092923 livalo Drugs 0.000 description 1
• 238000012317 liver biopsy Methods 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• MPAZKXHCZWDZDY-FFNUKLMVSA-L magnesium;(e,3r,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound [Mg+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 MPAZKXHCZWDZDY-FFNUKLMVSA-L 0.000 description 1
• 238000002595 magnetic resonance imaging Methods 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 231100000682 maximum tolerated dose Toxicity 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 210000002752 melanocyte Anatomy 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 210000000716 merkel cell Anatomy 0.000 description 1
• 230000007102 metabolic function Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 230000015689 metaplastic ossification Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 238000012900 molecular simulation Methods 0.000 description 1
• 150000004712 monophosphates Chemical class 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 238000002887 multiple sequence alignment Methods 0.000 description 1
• 230000004092 musculoskeletal function Effects 0.000 description 1
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 229940063121 neoral Drugs 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 230000007971 neurological deficit Effects 0.000 description 1
• 230000007658 neurological function Effects 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 208000018360 neuromuscular disease Diseases 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 230000007171 neuropathology Effects 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 230000037434 nonsense mutation Effects 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 231100000862 numbness Toxicity 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• 239000002859 orphan drug Substances 0.000 description 1
• 229940000673 orphan drug Drugs 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 230000002188 osteogenic effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 210000002990 parathyroid gland Anatomy 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 230000002974 pharmacogenomic effect Effects 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 229960002797 pitavastatin Drugs 0.000 description 1
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
• RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 108010094020 polyglycine Proteins 0.000 description 1
• 229920000232 polyglycine polymer Polymers 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 230000000379 polymerizing effect Effects 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 108091033319 polynucleotide Proteins 0.000 description 1
• 102000040430 polynucleotide Human genes 0.000 description 1
• 239000002157 polynucleotide Substances 0.000 description 1
• 239000001205 polyphosphate Substances 0.000 description 1
• 235000011176 polyphosphates Nutrition 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229940089484 pravachol Drugs 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 238000009597 pregnancy test Methods 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 208000037821 progressive disease Diseases 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000012846 protein folding Effects 0.000 description 1
• 230000004853 protein function Effects 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 230000009325 pulmonary function Effects 0.000 description 1
• 238000009613 pulmonary function test Methods 0.000 description 1
• 210000003492 pulmonary vein Anatomy 0.000 description 1
• 230000035485 pulse pressure Effects 0.000 description 1
• 230000001696 purinergic effect Effects 0.000 description 1
• 238000002601 radiography Methods 0.000 description 1
• 230000009103 reabsorption Effects 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 210000002254 renal artery Anatomy 0.000 description 1
• 229940017164 repatha Drugs 0.000 description 1
• 238000009256 replacement therapy Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 229940061969 rheumatrex Drugs 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• 229960000672 rosuvastatin Drugs 0.000 description 1
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
• 229940063122 sandimmune Drugs 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 238000002864 sequence alignment Methods 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 238000011947 six minute walk test Methods 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 231100001055 skeletal defect Toxicity 0.000 description 1
• 210000004927 skin cell Anatomy 0.000 description 1
• 206010040882 skin lesion Diseases 0.000 description 1
• 231100000444 skin lesion Toxicity 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 239000000243 solution Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000003319 supportive effect Effects 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 238000012353 t test Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 108060008226 thioredoxin Proteins 0.000 description 1
• 229940094937 thioredoxin Drugs 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 208000021510 thyroid gland disease Diseases 0.000 description 1
• 210000002303 tibia Anatomy 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 210000003371 toe Anatomy 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 208000032349 type 2B vitamin D-dependent rickets Diseases 0.000 description 1
• 230000004222 uncontrolled growth Effects 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 210000000689 upper leg Anatomy 0.000 description 1
• 238000002562 urinalysis Methods 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 238000002255 vaccination Methods 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 238000011100 viral filtration Methods 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
• 235000005282 vitamin D3 Nutrition 0.000 description 1
• 239000011647 vitamin D3 Substances 0.000 description 1
• 229940021056 vitamin d3 Drugs 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 210000000707 wrist Anatomy 0.000 description 1